Median Increase Research Articles

Randomized Controlled Trial of Intravenous Ferric Carboxymaltose vs Oral Iron to Treat Iron Deficiency Anemia After Variceal Bleed in Patients With Cirrhosis.

Limited evidence exists on the optimal strategy to correct iron deficiency anemia after variceal bleeding (VB) in cirrhosis. This trial compared the efficacy and safety of intravenous ferric carboxymaltose (IV-FCM) with those of oral iron therapy in this cohort. In this open-label, single-center, randomized controlled trial, eligible patients with hemoglobin <10 g/dL and iron deficiency (ferritin <100 ng/mL) after VB received either IV-FCM (1,500-2,000 mg) divided into 2 doses (n = 48) or oral carbonyl iron (100 mg elemental iron/day) (n = 44) for 3 months. The primary outcome was change in hemoglobin at 3 months. Secondary outcomes included improvement in anemia (last hemoglobin >12 g/dL), normalization of iron stores (ferritin >100 ng/mL), liver-related adverse events, adverse drug reactions, and changes in quality of life (CLDQOL questionnaire). Baseline characteristics, including median Child-Turcotte-Pugh score 7 (interquartile range [IQR] 6-9), Model for End-Stage Liver Disease score 12 (IQR 10-17), blood hemoglobin (8.25 ± 1.06 g/dL), and ferritin (30.00 ng/mL [15.00-66.50]), were comparable in both arms. The median increase in hemoglobin at 3 months in the IV and oral arms was 3.65 g/dL (IQR 2.55-5.25) and 1.10 g/dL (IQR 0.05-2.90 g/dL) ( P < 0.001), respectively. Iron stores normalized in 84.6% and 21% of the IV and oral arms, respectively ( P < 0.001). Anemia improved in 50% and 21.9% in the IV and oral arms, respectively ( P < 0.009). Patients in the IV arm showed a significant improvement in all domains of CLDQOL. Liver-related adverse events were comparable in both arms. Transient mild/moderate hypophosphatemia developed in 43% of patients receiving IV-FCM. Intravenous iron replacement is efficacious and safe to treat iron deficiency anemia after VB in patients with cirrhosis.

The Utility of Virtual Home Visits to Reduce Asthma Burden in Low-Income Black Communities in Louisiana During the COVID-19 Pandemic.

The Louisiana Department of Health identified a need for greater outreach in low-income Black communities that addressed environmental asthma triggers. We piloted an asthma virtual home visit (VHV) program and evaluated its reach and ability to promote asthma self-management strategies in communities with a high prevalence of poorly controlled asthma. Participants from Louisiana were continuously recruited into the VHV program starting in March 2021 and provided with asthma education materials. Participants reporting poorly controlled asthma and environmental triggers were also offered 3 VHVs with a respiratory therapist. All participants were asked to complete a preintervention and postintervention knowledge test, an Asthma Control Test (ACT) (maximum score = 25; scores ≤19 indicate poorly controlled asthma), and a final survey that assessed perceptions about asthma management and reduction of environmental triggers. As of October 2022, 147 participants were enrolled in the program, and 52 had consented to and received ≥1 VHV. Forty VHV recipients (77%) were aged <18 years, 40 (77%) were Black people, and 46 (88%) were from families with extremely low or low incomes. Asthma symptoms improved across all participants, with a median increase of 2.4 points on the ACT. Knowledge tests revealed that 86% of participants learned about ≥1 new asthma trigger; a larger percentage of VHV recipients than nonrecipients (68% vs 36%) had an improved knowledge test score postintervention. Compared with preintervention, about three-quarters of participants reported feeling more empowered to self-manage their asthma and a significant improvement in their quality of life postintervention. The program provided virtual asthma education to communities with a high burden of asthma and improved asthma outcomes for participants. Similar virtual models can be used to promote health equity, especially in areas with limited access to health care.

Vehicle-Integrated Photovoltaics—A Case Study for Berlin

Recent developments in vehicle-integrated photovoltaics (VIPV) offer prospects for enhancing electric vehicle range, lowering operating costs, and supporting carbon-neutral transport, particularly in urban settings. This study evaluates the solar energy potential of parking spaces in Berlin, considering challenges like building and tree shading using digital surface models and weather data for solar simulations. Utilizing open datasets and software, the analysis covered 48,827 parking spaces, revealing that VIPV could extend vehicle range by 7 to 14 km per day, equating to a median annual increase of 2527 km. The findings suggest median yearly cost savings of 164 euros from reduced grid charging. However, the environmental benefits of solar vehicle charging were found to be less than those of traditional grid-connected photovoltaic systems. The study introduces a method to pinpoint parking spaces that are most suitable for solar charging.

Association of Phase Angle Dynamics with Sarcopenia and Activities of Daily Living in Osteoporotic Fracture Patients.

This study aimed to determine whether changes in phase angle during rehabilitation are associated with clinical outcomes such as activities of daily living (ADL), skeletal muscle mass index (SMI), and strength in patients with osteoporotic fractures. This retrospective observational study included patients with osteoporotic fractures admitted to convalescent rehabilitation wards. Changes in phase angle were defined as the difference between the phase angle values at discharge and on admission. The primary outcome was the Functional Independence Measure motor (FIM-motor) score at discharge. The secondary outcomes were SMI and handgrip strength at discharge. We used multivariate analysis to adjust for confounding factors and examine the association between changes in the phase angle and outcomes. We analyzed a total of 115 patients (97 women, mean age of 81.0±10.0 years), with a median change in phase angle of 0° during hospitalization. We observed increased phase angles in 49 patients (43%), with a median increase of 0.2°. Multiple regression analysis showed that changes in phase angle were independently associated with FIM-motor score at discharge (β=0.238, p=0.027). Changes in phase angle were not significantly associated with SMI (β=0.059, p=0.599) or handgrip strength (β=-0.032, p=0.773) at discharge. An increased phase angle during rehabilitation was positively associated with ADL improvement in patients with osteoporotic fractures. These findings may help clinicians make informed decisions regarding patient care and treatment strategies for better outcomes.

Prediction of the Individual Aortic Stenosis Progression Rate and its Association With Clinical Outcomes

BackgroundThe progression rate of aortic stenosis differs between patients, complicating clinical follow-up and management. ObjectivesThis study aimed to identify predictors associated with the progression rate of aortic stenosis. MethodsIn this retrospective longitudinal single-center cohort study, all patients with moderate aortic stenosis who presented between December 2011 and December 2022 and had echocardiograms available were included. The individual aortic stenosis progression rate was calculated based on aortic valve area (AVA) from at least 2 echocardiograms performed at least 6 months apart. Baseline factors associated with the progression rate of AVA were determined using linear mixed-effects models, and the association of progression rate with clinical outcomes was evaluated using Cox regression. ResultsThe study included 540 patients (median age 69 years and 38% female) with 2,937 echocardiograms (median 5 per patient). Patients had a linear progression with a median AVA decrease of 0.09 cm2/y and a median peak jet velocity increase of 0.17 m/s/y. Rapid progression was independently associated with all-cause mortality (HR: 1.77, 95% CI: 1.26-2.48) and aortic valve replacement (HR: 3.44, 95% CI: 2.55-4.64). Older age, greater left ventricular mass index, atrial fibrillation, and chronic kidney disease were associated with a faster decline of AVA. ConclusionsAVA decreases linearly in individual patients, and faster progression is independently associated with higher mortality. Routine clinical and echocardiographic variables accurately predict the individual progression rate and may aid clinicians in determining the optimal follow-up interval for patients with aortic stenosis.

Ophthalmology workforce over a decade in the Kingdom of Saudi Arabia: demographics, distribution, and future challenges

BackgroundThe ophthalmology workforce is an integral component of any health care system. However, the demand for eye care has imposed a heavy burden on this system. Hence, this study aimed to estimate the trends, demographic characteristics, distribution, and variation between Saudi and non-Saudi ophthalmologists and the future challenges of the ophthalmology workforce in the Kingdom of Saudi Arabia (KSA).MethodsThis study was conducted in the KSA and included ophthalmologists practicing from 2010 to 2023. From the Saudi Commission for Health Specialties, we obtained the number, gender, nationality, and rank of ophthalmologists. The geographic distribution of ophthalmologists in the KSA was obtained from the Ministry of Health Statistical Yearbook 2021.ResultsAs of January 2023, the KSA had a total of 2608 registered ophthalmologists, with approximately 81.06 ophthalmologists per 1,000,000 people. Only 38% of all ophthalmologists in the country were Saudis. The percentage of Saudi female graduates increased from 13.3% to 37.2% over 12 years [Sen’s estimator of slope for median increase per year = 1.33 (95% CI 1.22–1.57) graduates; trend test P < 0.001). Additionally, we found that the geographic distribution of ophthalmologists varied (test for homogeneity of rates, P < 0.0001), with the larger regions having a higher concentration of ophthalmologists than the smaller regions (75.6 in Riyadh versus 42.8 in Jazan per 1,000,000 people). However, the World Health Organization's target for the ophthalmologist-to-population ratio has been achieved in all 13 health regions of KSA.ConclusionThe recommended ophthalmologist-to-population ratio has been achieved in the KSA, and the number of Saudi ophthalmologists has almost doubled over the past 8 years. However, the majority of ophthalmologists are still non-Saudi, as Saudi ophthalmologists constitute approximately one-third of the ophthalmology workforce in the KSA. The geographical distribution of ophthalmologists varies, which might affect access to care in peripheral regions. In response to the growing demand for eye care in the KSA, several more effective measures might need to be considered.

Combined benthic and stream edge sampling better represent macroinvertebrate assemblages than benthic sampling alone along an aridity gradient

AbstractStudies of stream macroinvertebrates traditionally use sampling methods that target benthic habitats. These methods could underestimate biodiversity if important assemblage components exist outside of the benthic zone. To test the efficacy of different sampling methods, we collected paired reach‐wide benthic and edge samples from up to 10 study reaches in nine basins spanning an aridity gradient across the United States. Edge sampling targeted riparian‐adjacent microhabitats not typically sampled, including submerged vegetation, roots, and overhanging banks. We compared observed richness, asymptotic richness, and assemblage dissimilarity between benthic samples alone and different combinations of benthic and edge samples to determine the magnitude of increased diversity and assemblage dissimilarity values with the addition of edge sampling. We also examined how differences in richness and assemblage composition varied across an aridity gradient. The addition of edge sampling significantly increased observed richness (median increase = 29%) and asymptotic richness (median increase = 173%). Similarly, median Bray–Curtis dissimilarity values increased by as much as 0.178 when benthic and edge samples were combined. Differences in richness metrics were generally higher in arid basins, but assemblage dissimilarity either increased or decreased across the aridity gradient depending on how benthic and edge samples were combined. Our results suggest that studies that do not sample stream edges may significantly underestimate reach diversity and misrepresent assemblage compositions, with effects that can vary across climates. We urge researchers to carefully consider sampling methods in field studies spanning climatic zones and the comparability of existing data sets when conducting data synthesis studies.

Novel multiparametric MRI detects improved future liver remnant quality post-dual vein embolization

BackgroundOptimisation of the future liver remnant (FLR) is crucial to outcomes of extended liver resections. This study aimed to assess the quality of the FLR before and after dual vein embolization (DVE) by quantitative multiparametric MRI. MethodsOf 100 patients with liver metastases recruited in a clinical trial (Precision1:NCT04597710), ten consecutive patients with insufficient FLR underwent quantitative multiparametric MRI pre- and post-DVE (right portal and hepatic vein). FLR volume, liver fibro-inflammation (corrected T1) scores and fat percentage (proton density fat fraction, PDFF) were determined. Patient metrics were compared by Wilcoxon signed-rank test and statistical analysis done using R software. ResultsAll patients underwent uncomplicated DVE with improvement in liver remnant health, median 37 days after DVE: cT1 scores reduced from median (interquartile range) 790 ms (753–833 ms) to 741 ms (708–760 ms) p = 0.014 [healthy range <795 ms], as did PDFF from 11% (4–21%), to 3% (2–12%) p = 0.017 [healthy range <5.6%]. There was a significant increase in median (interquartile range) FLR volume from 33% (30–37%)% to 49% (44–52%), p = 0.002. ConclusionThis non-invasive and reproducible MRI technique showed improvement in volume and quality of the FLR after DVE. This is a significant advance in our understanding of how to prevent liver failure in patients undergoing major liver surgery.

Effect of Arterialization on Venous Blood Glucose Concentrations and Implications for Observed Continuous Glucose Monitoring Accuracy.

Background: Heating of the arm and/or hand ("arterialization") is sometimes used in continuous glucose monitoring (CGM) performance studies with the reported aim of reducing differences between venous and capillary glucose concentrations. In this study, the effect of heating on venous glucose concentrations and CGM accuracy was investigated. Methods: A heating pad set to 50°C (122°F) was used with 20 participants to heat either the dominant or nondominant arm and hand. Venous and capillary samples were obtained every 15 min on both arms throughout each of three 6-h glucose challenges. CGM sensors were worn on each upper arm for each of the three visits. Results: Heating of the arm led to a median increase in venous glucose concentrations of +1.4%. No similar effect on capillary concentrations was observed. As a result, the median capillary to venous difference decreased from +5.9% in the nonheated arm to +4.2% in the heated arm. CGM accuracy observed in this study was affected by the selection of heated venous, nonheated venous, or capillary glucose concentrations as comparator data. The heating effect was more pronounced with rapidly decreasing glucose concentrations. Temperatures on the skin did not exceed 40°C (104°F). No adverse events or protocol deviations were associated with the use of the heating pad. Conclusions: Heating of the arm led to a small increase in venous glucose concentrations, but venous concentrations did not reach the level of capillary glucose concentrations. CGM accuracy observed in this study varied depending on the selected comparator data. This study was registered at the German Clinical Trials Register (DRKS00031197).

Dermatology teaching for undergraduate medical students in clinical routine - a structured four-week curriculum.

Dermatology teaching is fundamental for the promotion of young colleagues in our specialty. However, traditional teaching methods are being scrutinized by students of the 'Generation Y and Z', which can pose new challenges for teaching institutions. We therefore aimed to assess the motivational impact and reception of a newly created four-week curriculum containing modernized teaching methods integrated into clinical routine. In this single-center study, 67 medical students completed this curriculum composed of weekly learning objectives including knowledge of morphological terms, 10 common dermatoses, communication and presentation skills. The participants provided information on their level of interest in dermatology each week as well as positive and negative aspects of the curriculum. During the curriculum a significant median increase in interest in dermatology was reported with no differences between the genders. Low initial interest could be improved, high initial interest maintained. Participants with an interest in scientific work (20.9%) were more motivated during the curriculum. The variety, quality of teaching and structure were the main aspects rated positively. Suggestions for improvement included the need for more teaching by senior doctors, transfer of responsibility, and a working environment updated to the latest technology standards. The presented curriculum was well received by the participants and allowed to better define learning preferences of new generations which can be helpful to modernize traditional teaching methods. Interest in scientific work could be a factor to identify students with a particularly strong interest in dermatology.

(327) Adverse Event Reporting in Testosterone Therapy Randomized Controlled Trials (RCT)

Abstract Introduction Testosterone (T) therapy (TTH) is associated with well recognized adverse events (AEs) such as: polycythemia (PCT), major adverse cardiac events (MACE), gynecomastia (GYN), worsening obstructive sleep apnea (OSA). Objective We aimed to critically analyze published TTH RCTs with regard to how well TTH AEs were reported. Methods A literature review was performed of all TTH RCTs listed on PUBMED that had been published between 1997-2021. We describe sample size, trial duration, industry funding, T assay used, baseline and on-treatment total and free T, TTH modality, and mean follow-up during the RCTs. We also describe the reporting of PCT, GYN, MACE, OSA and the definitions used in these RCTs. Results 29 trials were reviewed (Table 1), 55% reported on transdermal T, 41% intramuscular T, 7% enclomiphene, 7% human chorionic gonadotropin and 7% other oral treatments (aromatase inhibitor, tamoxifen). 17% compared two TTH modalities. Median sample size was 73 [41, 189]. Median age was 63 [58, 67] years. Median follow-up in the RCT reported was 8 [6, 12] months. 55% had the support of pharmaceutical companies. The total T (TT) assay used was immunoassay (IA 59%), LCMS (24%), other (10%), while 7% did not report on the assay type, and only 55% reported free T level (79% calculate by Vermeulen formula, and 21% equilibrium dialysis). Median baseline TT level was 248 [227, 320] ng/dL; on TTH it was 528 [460, 621] ng/dL. Median baseline free T level was 5.4 [5, 6.3] ng/dL, on TTH it was 11.1 [9.3, 15.5] ng/dL. 83% measured HCT levels at any point, only 21% reported baseline levels, 24% reported post treatment. Median baseline HCT 43 [42, 46]%, post-TTH median HCT increase of 2.4[-2.5, +3]%. 52% reported on PCT rates (45% defined HCT &amp;gt;52%, 7% HB &amp;gt;17 g/dL). Median PCT rate was 2%, none mentioned phlebotomy. 17% of RCTs reported on GYN, with a median rate of 1.5%, while none mentioned GYN grade or if mammography had been performed. 17% of trials mentioned MACE, but only 2 defined MACE. Median MACE rate was 2%. 10% reported OSA, but none mentioned the type of assessment; the median rate was OSA 2%. Conclusions This analysis showed that the majority TTH RCTs have sub-optimal reporting of TTH safety. Disclosure No.

A novel composition of endogenous metabolic modulators improves red blood cell properties in sickle cell disease.

The most common forms of sickle cell disease (SCD) are sickle cell anemia (SCA; HbSS) and HbSC disease. In both, especially the more dense, dehydrated and adherent red blood cells (RBCs) with reduced deformability are prone to hemolysis and sickling, and thereby vaso-occlusion. Based on plasma amino acid profiling in SCD, a composition of 10 amino acids and derivatives (RCitNacQCarLKHVS; Axcella Therapeutics, USA), referred to as endogenous metabolic modulators (EMMs), was designed to target RBC metabolism. The effects of ex vivo treatment with the EMM composition on different RBC properties were studied in SCD (n=9 SCA, n=5 HbSC disease). Dose-dependent improvements were observed in RBC hydration assessed by hemocytometry (MCV, MCHC, dense RBCs) and osmotic gradient ektacytometry (Ohyper). Median (interquartile range [IQR]) increase in Ohyper compared to vehicle was 4.9% (4.0%-5.5%), 7.5% (6.9%-9.4%), and 12.8% (11.5%-14.0%) with increasing 20×, 40×, and 80X concentrations, respectively (all p<0.0001). RBC deformability (EImax using oxygen gradient ektacytometry) increased by 8.1% (2.2%-12.1%; p=0.0012), 9.6% (2.9%-15.1%; p=0.0013), and 13.3% (5.7%-25.5%; p=0.0007), respectively. Besides, RBC adhesion to subendothelial laminin decreased by 43% (6%-68%; p=0.4324), 58% (48%-72%; p=0.0185), and 71% (49%-82%; p=0.0016), respectively. Together, these results provide a rationale for further studies with the EMM composition targeting multiple RBC properties in SCD.

Measuring cough-related quality of life and cough frequency in pulmonary TB.

BACKGROUND: Cough is the key symptom of pulmonary TB (PTB) and is associated with transmission. No tool for measuring the subjective impact of cough in PTB has been previously validated. We sought to measure patientreported cough in PTB and investigate any relationship to objectively quantified daily cough frequency.METHODS: The validity of the Leicester Cough Questionnaire (LCQ) was assessed in sequential patients newly diagnosed with PTB at a UK hospital. Resulting LCQ scores were compared to non-cough clinical variables, and to 24-h, ambulatory, objective cough frequency measured using the Leicester Cough Monitor.RESULTS: The LCQ in 30 patients with PTB was acceptable to users and had high internal reliability (Cronbach's α = 0.93), concurrent validity (correlation with visual analogue scale for cough severity, Spearman's ρ = ???0.69) and responsiveness (substantial median increase score after 2 weeks of TB treatment: 5.1 points, IQR 1.8???9.7; P = 0.003). There was only moderate correlation between patient-reported cough and objectively-measured 24-h cough frequency in PTB (ρ = ???0.48, P = 0.008).CONCLUSION: The LCQ is valid for use in PTB, with applications that include monitoring treatment of the disease. However, there was a mismatch between objective and subjective assessment of cough, which has important implications for delayed diagnosis and transmissibility.

The Impact of Climate Change on Construction Activity Performance

There are specific construction operations that require weather forecast data to make short-term decisions regarding construction; however, most resource-related decision making and all project management plans must be carried out to anticipate weather conditions beyond the capabilities of the currently available forecasting technologies. In this study, a series of single- and multi-risk analyses were performed with ~9 km grid resolution over Türkiye using combinations of weather and climate variables and their threshold values which have an impact on the execution and performance of construction activities. These analyses will improve the predictability of potential delays, enable the project to be scheduled on a future-proof basis by considering the calculated normal and periodic predictions on the grid scale, and serve as a dispute resolution tool for related claims. A comprehensive case study showcasing the methodology and illustrating its application shows that the project duration is expected to be extended because of the impact of climate on both historical and future periods. While the original project duration was 207 days, when climate effects were considered, the optimum mean and median values increased to 255 and 238 days, respectively, for the historical period. The optimum duration mean and median change to 239 days by the end of the century, according to the SSP5-8.5 scenario, if the construction schedules consider climate change. The change in duration was mainly due to rising temperatures, which increased winter workability and reduced summer workability. However, if the historical practices are carried over to future schedules, the mean and median increase to 258 days and 244 days, respectively, which may cause unavoidable direct, indirect, or overhead costs.

The role of online MR-guided multi-fraction stereotactic ablative radiotherapy in lung tumours

BackgroundThe aim of this prospective observational study was to evaluate the dosimetry benefits, changes in pulmonary function, and clinical outcome of online adaptive MR-guided SBRT. MethodsFrom 11/2020–07/2022, 45 consecutive patients with 59 lesions underwent multi-fraction SBRT (3–8 fractions) at our institution. Patients were eligible if they had biopsy-proven NSCLC or lung cancer/metastases diagnosed via clinical imaging. Endpoints were local control (LC) and overall survival (OS). We evaluated PTV/GTV dose coverage, organs at risk exposure, and changes in pulmonary function (PF). Acute toxicity was classified per the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0. ResultsThe median PTV was 14.4 cm3 (range: 3.4 – 96.5 cm3). In total 195/215 (91%) plans were reoptimised. In the reoptimised vs. predicted plans, PTV coverage by the prescribed dose increased in 94.6% of all fractions with a median increase in PTV VPD of 5.6% (range: −1.8 – 44.6%, p < 0.001), increasing the number of fractions with PTV VPD ≥ 95% from 33% to 98%. The PTV D95% and D98% (BED10) increased in 93% and 95% of all fractions with a median increase of 7.7% (p < 0.001) and 10.6% (p < 0.001). The PTV D95% (BED10) increased by a mean of 9.6 Gy (SD: 10.3 Gy, p < 0.001). At a median follow-up of 21.4 months (95% CI: 12.3–27.0 months), 1- and 2-year LC rates were 94.8% (95% CI: 87.6 – 100.0%) and 91.1% (95% CI: 81.3 – 100%); 1- and 2-year OS rates were 85.6% (95% CI: 75.0 – 96.3%) and 67.1 % (95% CI: 50.3 – 83.8%). One grade ≥ 3 toxicity and no significant reduction in short-term PF parameters were recorded. ConclusionsOnline adaptive MR-guided SBRT is an effective, safe and generally well tolerated treatment option for lung tumours achieving encouraging local control rates with significantly improved target volume coverage.

Ascorbic acid deficiency amongst spondylodiscitis patients.

Spondylodiscitis can be a disabling and life-threatening infection. Ascorbic Acid is crucial for neutrophil function and collagen formation. Its association and clinical relevance in spondylodiscitis has not been previously examined. To determine the prevalence, characteristics, and clinical outcomes of spondylodiscitis patients with Ascorbic Acid deficiency. Sixty-eight consecutive patients admitted with spondylodiscitis, between December 2021 and August 2023 were included. Clinical characteristics, Ascorbic Acid levels and clinical outcomes were evaluated. Thirty-seven patients had Ascorbic Acid levels taken during admission. The median initial Ascorbic Acid level was 15 μmol/L with an IQR 6.5-27 μmol/L. Depletion defined as <28 μmol/L was present in 78% of patients. Deficiency defined as ≤11 μmol/L was present in and 46% of patients. Patients with depletion were more likely to require Intensive Care Admission (absolute risk increase = 24.1%; 2.6%-45.7%). Fifteen patients had repeat serum levels taken during admission with median increase of 17 μmol/L and an IQR 0-26 μmol/L. Patients that received supplementation had a significantly greater increase in Ascorbic Acid levels compared with those that did not receive supplementation (P = 0.002). Ascorbic acid deficiency is highly prevalent amongst spondylodiscitis patients. Depletion was associated with worse outcomes. Replacement significantly increased serum levels in comparison to standard hospital diet. The clinical significance of replacement remains to be evaluated.

Differences in the association between epidural analgesia and length of stay by surgery type: an observational study

IntroductionDespite a decline in the use of thoracic epidural analgesia related in part to concerns for delayed discharge, it is unknown whether changes in length of stay (LOS) associated with...

Rural general practitioner confidence in diagnosing and managing dementia: A two-stage, mixed methods study of dementia-specific training.

Dementias a prevalent chronic healthcare condition affecting 46 million people worldwide and projected to grow in the coming years. Australians living in rural and regional areas often lack access to specialist dementia care, despite greater prevalence relative to metropolitan areas. This study aimed to explore general practitioners (GP) understanding, confidence and attitudes towards dementia management in the rural context, and design and pilot a dementia-specific training program. A two-stage, mixed methods design, using qualitative and quantitative methods. Sixteen regional GPs from across Victoria participated in scoping semi-structured interviews. Fourteen separate GPs in the St Anthony Family Medical Practice group in the regional Loddon-Mallee area of Victoria completed the pilot training intervention. Pre- and post-training surveys (n = 10), as well as post-training interviews (n = 10), assessed attitude and knowledge changes. Analysis of semi-structured scoping interviews indicated three themes regarding experience of dementia management, including: (1) attitudes to and experiences of dementia; (2) supporting people living with dementia; and (3) knowledge, education and training of dementia. The pilot dementia-specific training was found to improve attitudes (agreement across 24 best-practice indicators improved from 30% to 79%), knowledge (median increase of 2.5/10) and confidence in managing dementia and disclosing dementia diagnoses (median increase 3/10 and 2.75/10, respectively). General practitioners in this study lacked initial confidence in detecting and managing dementia in a rural primary care setting. A targeted training program showed improvements in these areas. Accessible, locally delivered, dementia education has the potential to improve confidence in early detection and management of people with dementia and thereby may address gaps in access to care for people living with dementia in rural settings.

Enrichment of circulating helper-T (Th) and unswitched memory-B (NSwM-B) cell populations and responsiveness to immune checkpoint blockade (ICB) in microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) colorectal cancer (CRC).

150 Background: The anti-tumor activity of ICB in MSS/pMMR-CRC is limited. However, recent studies have highlighted the possibility of inducing ICB responsiveness by oxaliplatin-based chemotherapy. The understanding of underlying mechanisms and identification of rational biomarkers are major focus areas in immuno-oncology. Methods: Patients with previously untreated, unresectable abdominal metastases from MSS/pMMR-CRC were randomly assigned to the oxaliplatin-based standard Nordic FLOX regimen (control arm) or 2 FLOX cycles followed by 2 ICB (nivolumab) cycles in a repeat sequential schedule (experimental arm). Radiologic response assessment was done every 8 weeks, and the study arms reached identical primary endpoint – median progression-free survival (PFS) 9.3 months. Experimental-arm patients at one study center had peripheral blood mononuclear cells (PBMC) prepared at study entry (V1), after the initial 2 FLOX cycles (V3), and after the succeeding 2 nivolumab cycles (V5). The PBMC were incubated with 19 cell-surface antibodies and analyzed by mass cytometry. Patients were categorized in PFS &gt;9.3 months (improved; n = 7) or PFS &lt;9.3 months (shortened; n = 6). Live cell clusters were identified by hierarchically applying automated 1D gates to the available lineage markers. After gating, all cells were assigned to soft clusters according to phenotypes. The cluster sizes were used to compute the differential abundance of immune-cell populations and a Peacock test assessed multivariate changes between the improved and shortened PFS groups. Results: Circulating CD4+ (Th) cells and CD27+IgD+ (NSwM-B) cells were concurrently enriched in the improved PFS group. After the initial 2 FLOX cycles (V3), median increase (from V1) was 2.89% (of lymphocyte count) for Th cells and 0.54% (of leukocyte count) for NSwM-B cells (p &lt; 0.001). Continued responses occurred over the succeeding 2 nivolumab cycles (until V5) with median increase of 1.19% for Th cells and 0.19% for NSwM-B cells (p &lt; 0.001). The association between the immune-cell alterations and PFS was validated by categorizing the cases in above or below the median increase in Th and NSwM-B cell populations from V1 to V5. The high-increase group achieved median PFS 15.0 months (95% CI, 10.8-19.2) compared to 4.0 months (95% CI, 1.9-22.1) for the low-increase group (log-rank; p = 0.002). Conclusions: This unsupervised analysis of high-dimensional PBMC data from a limited case number revealed that circulating Th and NSwM-B cell populations may mediate ICB responsiveness invoked by short-course oxaliplatin-based chemotherapy in patients with abdominal metastases from MSS/pMMR-CRC. Owing to weaknesses of such a post-hoc analysis, further studies are needed to confirm the generalizability of these findings. Clinical trial information: NCT003388190 .

Flow-based immunomagnetic enrichment of circulating tumor cells from diagnostic leukapheresis product.

The clinical utility of circulating tumor cells (CTCs) is hampered by the low number of cells detected. Diagnostic leukapheresis (DLA) offers a solution but, due to the observed non-specific binding and clumping, processing of DLA samples using the CellSearch system only allows for the processing of aliquots consisting of ~ 2% of the total DLA sample per test. Here, we introduce a flow enrichment target capture Halbach-array (FETCH)-based separation method in combination with a DNase preprocessing step to capture CTCs from larger fractions of DLA products without clumping. To evaluate the FETCH method, we processed peripheral blood samples from 19 metastatic castration-naïve prostate cancer (mCNPC) patients with CellSearch, and processed 2% aliquots of leukapheresis samples from the same patients with CellSearch as well as FETCH with or without DNase preprocessing. Using 2% aliquots from six patients, the use of FETCH with fewer immunomagnetic epithelial cellular adhesion molecule (EpCAM) conjugated ferrofluids was tested, whereas 20% aliquots from four patients were used to evaluate the processing of 10-fold larger DLA samples using FETCH. Results show that the cell clumping normally seen after immunomagnetic enrichment of DLA material was greatly reduced with the use of DNase pretreatment, while the number of CTCs detected was not affected. The number of CTCs detected in 2% aliquots of DLA using FETCH was unchanged compared to CellSearch and did not decrease when using down to 10% of the volume of immunomagnetic anti-EpCAM ferrofluids normally used in a CellSearch test, whereas the number of co-enriched white blood cells reduced a median 3.2-fold. Processing of a 20% aliquot of DLA with FETCH resulted in a 14-fold increase in CTCs compared to the processing of 2% aliquots of DLA using CellSearch and a total 42-fold median increase in CTCs compared to peripheral-blood CellSearch.